Renal replacement therapy in patients with acute respiratory distress syndrome: a single-center retrospective study.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) who develop acute kidney injury have increased mortality and frequently require renal replacement therapy (RRT). The optimal timing for initiation of RRT after onset of ARDS to improve survival is not known. METHODS: We retrospectively reviewed clinical data on patients admitted to our health system over a 2-year period. Individual charts were carefully reviewed to ascertain that patients met the Berlin criteria for ARDS and to categorize RRT utilization. The Kaplan-Meier analysis was conducted to compare early (£48 hours postintubation) versus late (>48 hours postintubation) initiation of RRT. Associations between RRT initiation and mortality were evaluated using Cox proportional hazards regression. RESULTS: A total of 75 patients were identified with ARDS, 95% of whom received RRT. Mortality of patients who required RRT was 56%. The main indications for RRT initiation were fluid overload (75%), metabolic acidosis (64%), and hyperkalemia (33%). The Kaplan-Meier analysis comparing early initiation of RRT to late initiation of RRT showed no survival benefit. Cox proportional hazard models testing the association between timing of RRT initiation with survival and adjusting for sex, race, ethnicity, and Acute Physiology and Chronic Health Evaluation II score did not reach statistical significance (HR=0.94, 95% CI=0.48-1.86). CONCLUSION: Timing of RRT initiation was not associated with a survival benefit. Prospective study in the utilization and outcomes of RRT in ARDS could assist in optimizing its usage in this population.

Pulmonary Embolism with Right Ventricular Dysfunction: Who Should Receive Thrombolytic Agents?

BACKGROUND: Appropriate management of pulmonary embolism patients with right ventricular dysfunction is uncertain. Recent guidelines have stressed the need for more data on the use of thrombolytic agents in the stable pulmonary embolism patient with right ventricular dysfunction. The objective of this study is to investigate the hypothesis that thrombolytic therapy in hemodynamically stable pulmonary embolism patients with right ventricular dysfunction is not associated with improved mortality. METHODS: We did a retrospective analysis using multi-institutional observational data from the Nationwide Inpatient Sample database. International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes were used to identify the patients with pulmonary embolism and right ventricular dysfunction. In-hospital mortality was defined as the primary outcome of interest. RESULTS: Over the 4 years of the study period, 3668 patients with right ventricular dysfunction and pulmonary embolism were found, of which 3253 patients were identified as having hemodynamically stable right-sided heart failure with pulmonary embolism. There was no significant difference in mortality between hemodynamically stable pulmonary embolism patients with right ventricular dysfunction who received thrombolytic agents compared with those who did not. When outcomes were assessed for patients with right ventricular dysfunction and hemodynamic instability, a significant improvement in mortality was noted for patients with right ventricular dysfunction who received thrombolytic agents, which confirmed previous reports that thrombolytic therapy decreases mortality in pulmonary embolism patients who are hemodynamically unstable. CONCLUSION: Our data support the use of less aggressive treatment for stable pulmonary embolism patients with right ventricular dysfunction. These results argue against the reflexive use of thrombolytic agents in stable pulmonary embolism patients with right ventricular dysfunction.

Recruitment and retention of healthy and high-risk older adults for a multiyear influenza vaccination study.

PURPOSE: Evaluate five different recruitment strategies for their capacity to enroll and retain both healthy and vulnerable older adults as part of a multiyear influenza vaccination study. METHODS: We analyzed recruitment methods and other characteristics ofindividuals who participated in or were considered for five sequential one-year studies. RESULTS: Of 940 screened individuals, 820 met eligibility criteria with 795 enrolled over the five-year study (307 primary participants). Among these enrollees, 63.4% were female and 95.5% were white, with mean ages of 75.3 (older group) and 30.6 (younger group). More than a half (56.7%) of the participants enrolled more than once, participating an average of 2.56 (SD = 1.6) times. The majority (81.9%) of individuals recruited each year were return participants identified during earlier recruitments. Physician referrals resulted in only 5.3% recruitments. CONCLUSIONS: Recruitment and retention of study subjects, especially older adults, was facilitated by the existence ofa database listing past participants.

Differential gene expression of p27Kip1 and Rb knockout pituitary tumors associated with altered growth and angiogenesis.

Mice lacking the p27Kip1 Cdk inhibitor, like mice lacking Rb, develop pituitary tumors involving pars intermedia melanotrophs, yet p27(Kip1) tumors are genetically distinct from Rb derived tumors as they exhibit haploid insufficiency. We compared tumors from mice with p27( Kip1) constitutive and tissue specific null mutations to tumors arising in tissue specific Rb knockout mice with the aim of determining whether they are distinguished by quantitative or qualitative differences. The rate of p27Kip1 knockout tumor development was strongly influenced by strain background due to polygenic strain modifiers in the C57BL/6J versus 129S4 strains but, unlike a prior report of Rb mutants, this impacted tumor incidence but not the tumor spectrum. p27Kip1 tumors were oligoclonal or polyclonal based on studies of X-chromosomal inactivation of Dock11. In contrast, Rb null tissue developed monoclonal neoplasms even in the absence of a requirement for Rb mutant clonal selection. Rb null tumors exhibited a higher proliferation rate and developed ischemic necrosis associated with an aberrant vasculature. p27Kip1 null tumors maintained normal vascular density, through a tumor cell dependent mechanism, but were more often hemorrhagic. Gene expression profiles distinguished p27Kip1 from Rb null tumors including significant differences in expression of Rb and E2F signature genes. Rb null tumors expressed higher levels of VEGF which, in other systems, is associated with dilated vessels, ineffective perfusion and tissue hypoxia. Mouse models lacking p27Kip1 and Rb may help us better understand the pathophysiology of MEN syndromes, retinoblastoma and other cancers that disrupt these important cell cycle inhibitors.